Using the mouse skin model of tumor promotion in vivo and in vitro, we will investigate the relationship of phorbol ester alteration of epidermal growth factor binding to the induction of DNA synthesis. In studies employing cultures of mouse primary epidermal cells and Rat-1 fibroblasts cultures we will study the effect of tumor promotors on epidermal growth factor number and affinity using a 125I-epidermal growth factor alteration to the onset of DNA synthesis. DNA synthesis will be measued by gradient density analysis of semi-conservatively labeled DNA and by autoradiography. We will also investigate the effects of antipromoting protease inhibitors and anti-inflammatory steroids on the latter processes. Using the mouse skin model for tumor promotion in vivo, we will study the effects of tumor promoters and hyperplastic agents on the temporal distribution and binding of 125I-epidermal growth factor and the relationship of binding to DNA synthesis. The alteration of epidermal growth factor binding caused by phorbol esters in mouse skin will be studied using the 125I-epidermal growth factor radioreceptor assay. DNA synthesis will be measured by density gradient analysis of semiconservatively labeled DNA and by autoradiography. The ability of the antipromoting protease inhibitors and anti-inflammatory steroids to modify the epidermal growth factor receptors in mouse skin will also be studied.